Biomedical subjects

Lei Liu

Publications and source records attributed to Lei Liu.

At least 73 records · Page 4Linked to original sources

PubMed2005

Hydrophobic and electronic factors in the design of dialkylglycine decarboxylase mimics.

The first functional catalytic mimic of the enzyme dialkylglycine decarboxylase is described. This system utilizes a hydrophobically modified polyethylenimine polymer, a pyridoxamine cofactor, and a 2-aryl-2-alkylglycine sacrificial amine source to convert alpha-keto acids to alpha-amino acids at biologically relevant temperatures with multiple turnovers of the pyridoxamine catalyst. The effects of hydrophobic and electronic factors in the 2,2-disubstituted sacrificial amine source and the pyridoxamine catalyst on turnover frequency and turnover number are explored.

Catalysis↗

PubMed2005

Knowledge guided analysis of microarray data.

To microarray expression data analysis, it is well accepted that biological knowledge-guided clustering techniques show more advantages than pure mathematical techniques. In this paper, Gene Ontology is introduced to guide the clustering process, and thus a new algorithm capturing both expression pattern similarities and biological function similarities is developed. Our algorithm was validated on two well-known public data sets and the results were compared with some previous works. It is shown that our method has advantages in both the quality of clusters and the precision of biological annotations. Furthermore, the clustering results can be adjusted according to different stringency requirements. It is expected that our algorithm can be extended to other biological knowledge, for example, metabolic networks.

Algorithms↗

PubMed2005

Development of an ONIOM-G3B3 method to accurately predict C-H and N-H bond dissociation enthalpies of ribonucleosides and deoxyribonucleosides.

The roles of ribonucleoside and deoxyribonucleoside radicals in DNA and RNA damage cannot be properly understood in the absence of knowledge of the C-H and N-H bond dissociation enthalpies (BDEs) depicting the energy cost to generate each of these radicals. However, because the nucleoside radicals tend to be extremely short-lived and it is very difficult to separate and identify different nucleoside radicals, experimental BDEs for nucleosides have remained elusive. Herein, we developed an ONIOM-G3B3 method in order to reliably predict the BDEs of nucleosides and we carefully benchmarked this new method against over 60 experimental BDEs of diverse sizable molecules. It was found that the accuracy of the ONIOM-G3B3 method was about 1.4 kcal/mol for BDE calculations. Using the ONIOM-G3B3 method, a full scale of C-H and N-H BDEs were obtained for the first time for ribonucleosides and deoxyribonucleosides with an estimated error bar of +/-1.4 kcal/mol. Discussions were then made about the interesting connections between these BDE values and previously reported experimental observations concerning radical-mediated DNA and RNA lesions. The significance of the work is twofold: (i) Nucleosides represent one of the most important groups of compounds in science. A full scale of reliable bond dissociation enthalpies for nucleosides is of fundamental importance. (ii) This work demonstrates the feasibility to accurately predict the bond strength of various sizable molecules ranging from nanosize molecular devices to biologically significant compounds.

Carbon↗

PubMed2005

Gene expression profiling of 17beta-estradiol and genistein effects on mouse thymus.

Estrogen regulates thymic development and involution and modulates immune function. Despite its critical role in thymus, as well as in autoimmune disorders, the mechanism by which estrogen affects the thymus is not well understood. We previously reported that the estrogenic soy isoflavone genistein, as well as 17beta-estradiol (E2), could induce thymic involution, but genistein effects were only partially mediated through estrogen receptors. To provide insights into mechanisms of estrogenic effects in the thymus, we investigated thymic gene expression changes induced by E2 (125 ng/day) and genistein (1500 ppm in feed) in weanling mice using high-density DNA arrays. We identified several E2-responsive genes involved in thymic development and thymocyte signaling during selection and maturation. Functional characterization indicated effects on genes involved in transcription, apoptosis, and the cell cycle. This study also identified changes in several E2-regulated transcripts essential to maintain immune self-tolerance. E2 upregulated more genes than genistein, while genistein downregulated more genes than E2. Though each treatment regulated several genes not altered by the other, there was considerable overlap in the genes regulated by E2 and genistein. Changes in transcription factors and cell cycle factors were consistent with decreases in cell proliferation induced by both genistein and E2. As indicated by the regulation of non-E2-responsive genes, genistein also induced unique effects through non-estrogenic mechanisms. The specific downregulation of the CD4 coreceptor transcript by genistein was consistent with the decline of CD4+ thymocytes in genistein-treated mice in our previous study. This is the first study identifying E2 and genistein target genes in the thymus. These findings provide new mechanistic insights toward explaining estrogen action on thymocyte development, selection, and maturation, as well as the effects of genistein on prenatal and neonatal thymic development and function.

Animals↗

PubMed2005

[Effect of basic fibroblast growth factor on change of caspase 3 gene expression after distractive spinal cord injury in rats].

OBJECTIVE: To observe the effects of basic fibroblast growth factor (bFGF) on neuronal apoptosis and caspase 3 gene expression after spinal cord injury. METHODS: Forty-five SD rats were randomly divided into 3 equal groups: normal group (n = 5, with the spinal cord intact), treatment group [n = 20, with their spinal cord at T13-L2 injured by distraction till the cortical somatosensory evoked potential (CSEP) decreased by 70% and then a thin plastic tube inserted into the subarachnoid cavity below the injured level for perfusion of bFGF 20 microg immediately, and 1, 2, 3, 4, 8, 12, and 24 hours after injury], and control group (n = 20, with their spinal cord at T13-L2 injured by distraction till the CSEP decreased by 70% and then a thin plastic tube inserted into the subarachnoid cavity below the injured level for perfusion of normal saline of the same volume at the same time points). CSEP was tested by electrophysiological technique to record the latent time of P1 wave and the amplitude of P1-N1. Combined behavioral score (CBS) was used to evaluate the function of spinal cord, including motivation, sensation, reflex, and coordination of actions. The rats were killed at the days 1, 4, 7, 14, and 21 postoperatively. A segment of spinal cord T13-L2 1.5 cm long was taken out to be fixed and sliced. Flow cytometry was used to detect the neuronal cell apoptosis. Imunohistochemistry and TUNEL were used to examine the expression of caspase 3. RESULTS: The CBS value of the normal group was 0, and the CBS values at different time points of the treatment group were all lower than those of the control group (P < 0.05 or P < 0.05). The values of latent time of P1 wave 4 approximately 21 days after injury of the 2 injury groups were all longer than that of the normal group, those of the treatment group being significantly shorter than those of the control group. The values of P1-N1 amplitude 4 approximately 21 days after injury of the 2 injury groups were all lower than that of the normal group, those of the treatment group being significantly lower than those of the control group (P < 0.05 or P < 0.01). TUNEL showed that the apoptotic cell numbers at different time points of the 2 injury groups were lower than that of the normal group, those of the treatment group being significantly lower than those of the control group (P < 0.05 or P < 0.01). Immunohistochemistry showed that the numbers of caspase 3 positive cells at different time points of the 2 injury groups were all lower than that of the normal group, those of the treatment group being significantly lower than those of the control group (P < 0.05 or P < 0.01). The active fluorescence values at different time points of the 2 injury groups were all higher than those of the normal group, those of the treatment group being significantly lower than those of the control group (P < 0.05 or P < 0.01). CONCLUSION: bFGF inhibits the expression of caspase 3 protein, reduces the caspase 3 activity, lessens the secondary cell apoptosis in the injured spinal cord, and promotes nerve function recovery of spinal cord.

Animals↗

PubMed2005

Quantum-chemical predictions of absolute standard redox potentials of diverse organic molecules and free radicals in acetonitrile.

A calibrated B3LYP/6-311++G(2df,2p)//B3LYP/6-31+G(d) method was found to be able to predict the gas-phase adiabatic ionization potentials of 160 structurally unrelated organic molecules with a precision of 0.14 eV. A PCM solvation model was benchmarked that could predict the pK(a)'s of 15 organic acids in acetonitrile with a precision of 1.0 pK(a) unit. Combining the above two methods, we developed a generally applicable protocol that could successfully predict the standard redox potentials of 270 structurally unrelated organic molecules in acetonitrile. The standard deviation of the predictions was 0.17 V. The study demonstrated that computational electrochemistry could become a powerful tool for the organic chemical community. It also confirmed that the continuum solvation theory could correctly predict the solvation energies of organic radicals. Finally, with the help of the newly developed protocol we were able to establish a scale of standard redox potentials for diverse types of organic free radicals for the first time. Knowledge about these redox potentials should be of great value for understanding the numerous electron-transfer reactions in organic and bioorganic chemistry.

Journal Article↗

PubMed2005

A 7872 cDNA microarray and its use in bovine functional genomics.

The strategy used to create and annotate a 7872 cDNA microarray from cattle placenta and spleen cDNA sequences is described. This microarray contains approximately 6300 unique genes, as determined by BLASTN and TBLASTX similarity search against the human and mouse UniGene and draft human genome sequence databases (build 34). Sequences on the array were annotated with gene ontology (GO) terms, thereby facilitating data analysis and interpretation. A total of 3244 genes were annotated with GO terms. The array is rich in sequences encoding transcription factors, signal transducers and cell cycle regulators. Current research being conducted with this array is described, and an overview of planned improvements in our microarray platform for cattle functional genomics is presented.

Animals↗

PubMed2005

A study of inter-lab and inter-platform agreement of DNA microarray data.

As gene expression profile data from DNA microarrays accumulate rapidly, there is a natural need to compare data across labs and platforms. Comparisons of microarray data can be quite challenging due to data complexity and variability. Different labs may adopt different technology platforms. One may ask about the degree of agreement we can expect from different labs and different platforms. To address this question, we conducted a study of inter-lab and inter-platform agreement of microarray data across three platforms and three labs. The statistical measures of consistency and agreement used in this paper are the Pearson correlation, intraclass correlation, kappa coefficients, and a measure of intra-transcript correlation. The three platforms used in the present paper were Affymetrix GeneChip, custom cDNA arrays, and custom oligo arrays. Using the within-platform variability as a benchmark, we found that these technology platforms exhibited an acceptable level of agreement, but the agreement between two technologies within the same lab was greater than that between two labs using the same technology. The consistency of replicates in each experiment varies from lab to lab. When there is high consistency among replicates, different technologies show good agreement within and across labs using the same RNA samples. On the other hand, the lab effect, especially when confounded with the RNA sample effect, plays a bigger role than the platform effect on data agreement.

Animals↗

PubMed2005

Magic number silicon dioxide-based clusters: laser ablation-mass spectrometric and density functional theory studies.

The magic number silica clusters [(SiO(2))(n)O(2)H(3)](-) with n = 4 and 8 have been observed in the XeCl excimer laser (308 nm) ablation of various porous siliceous materials. The structural origin of the magic number clusters has been studied by the density functional theoretical calculation at the B3LYP/6-31G** level, with a genetic algorithm as a supplementary tool for global structure searching. The DFT results of the first magic number cluster are parallel to the corresponding Hartree-Fock results previously reported with only small differences in the structural parameters. Theoretical calculation predicts that the first magic number cluster (SiO(2))(4)O(2)H(4) and its anion [(SiO(2))(4)O(2)H(3)](-) will most probably take pseudotetrahedral cage-like structures. To study the structural properties of the second magic number cluster, geometries of the bare cluster (SiO(2))(8), the neutral complex cluster (SiO(2))(8)O(2)H(4), and the anionic cluster [(SiO(2))(8)O(2)H(3)](-) are fully optimized at the B3LYP/6-31G** level, and the corresponding vibrational frequencies are calculated. The DFT calculations predict that the ground state of the bare silica octamer (SiO(2))(8) has a linear chain structure, whereas the second magic number complex cluster (SiO(2))(8)O(2)H(4) and its anion [(SiO(2))(8)O(2)H(3)](-) are most probably a mixture of cubic cage-like structural isomers with an O atom inside the cage and several quasi-bicage isomers with high intercage interactions. The stabilization of these structures can also be attributed to the active participation of the group of atoms 2O and 4H (3H for the anion) in chemical bonding during cluster formation. Our theoretical calculation gives preliminary structural interpretation of the presence of the first and second magic number clusters and the absence of higher magic numbers.

Journal Article↗

PubMed2005

Substituent effects on the ring opening of 2-aziridinylmethyl radicals.

[reaction: see text] Substituent effects on the ring-opening reactions of 2-aziridinylmethyl radicals were studied systematically for the first time utilizing the ONIOM(QCISD(T)/6-311+G(2d,2p):B3LYP/6-311+G(3df,2p)) method. It was found that various substituents on the nitrogen atom had a relatively small effect on the ring opening of the 2-aziridinylmethyl radical. A pi-acceptor substituent at the C(1) position reduced the energy barrier for C-C cleavage dramatically, but it increased the energy barrier for C-N cleavage significantly at the same time. When the C(1) substituent is alkyl, the ring opening should always strongly favor the C-N cleavage pathway, regardless of whether the N substituent is alkyl, aryl, or COR. When the C(1) substituent is CHO (or CO-alkyl, CO-aryl, or CO-OR but not CO-NR(2)), the ring opening strongly favors the C-C cleavage pathway, regardless of whether the N substituent is alkyl, aryl, or COR. When the C(1) substituent is aryl (or alkenyl or alkynyl), the ring opening should favor the C-C cleavage pathway if the N substituent is alkyl or COR. If both the C(1) substituent and the N substituent are aryl, the ring opening should proceed via both the C-C and C-N cleavage pathways. The solvent effect on the regioselectivity of the ring opening of the 2-aziridinylmethyl radicals was found to be very small. The substituent effects on C-C cleavage could be explained successfully by the spin-delocalization mechanism. For the substituent effects on C-N cleavage, an extraordinary through-bond pi-acceptor effect must be taken into account. Furthermore, studies on bicyclic 2-aziridinylmethyl radicals showed that the ring strain could also affect the regiochemistry of the ring-opening reactions.

Journal Article↗

PubMed2005

Patterns of medication use in the RRI-CKD study: focus on medications with cardiovascular effects.

BACKGROUND: Patients with chronic kidney disease (CKD) stages 2-5 are known to suffer numerous complications and co-morbidities associated with kidney disease. The medication prescription patterns in this population are not well understood. We report on prescription data collected as part of a multicentre longitudinal study in patients with CKD, with a focus on medications with cardiovascular or cardioprotective effects. METHODS: Patients were recruited from four academic nephrology centres in the USA, with patient recruitment from June 2000 to March 2002. Medication data were captured at the time of first enrollment into the study. Individual medications were classified into medication groups, and those with predominant cardioprotective effects or for prevention of progression of kidney disease (e.g. medications for treatment of anaemia, lipid-lowering agents, antihypertensives, statins, etc.) were recorded for analysis. Descriptive statistics were used for medication prescription according to baseline demographics and co-morbidities. Predictors of epoetin and iron use were determined by logistic regression adjusting for age, race, sex, diabetes, glomerular filtration rate (GFR), haemoglobin and serum albumin. RESULTS: Medication data were available for 619 patients with stages 2-5 CKD. Patients were 60.6+/-16.0 years of age, and were prescribed 8+/-4 (range 1-28) medications. Overall, the proportion of patients prescribed different classes of medications included epoetin (20%), intravenous iron (13%), HMG-CoA reductase inhibitors (16%), angiotensin-converting enzyme (ACE) inhibitors (44%), angiotensin receptor blockers (13%), beta-blockers (46%), calcium channel blockers (52%) and aspirin (37%). There was a low use of epoetin (45%) and iron (20%) in patients with anaemia. Only 24% of patients with coronary artery disease were prescribed statins, and ACE inhibitors and angiotensin receptor blockers were used in only 58 and 23% of diabetic patients with proteinuria. Positive predictors of epoetin and iron therapy included white race and diabetes. Higher GFR and higher serum albumin were associated with lower odds of being prescribed epoetin. White race and diabetics were more likely to be prescribed iron. CONCLUSIONS: This study provides an overview of prescription practices in a cohort of CKD patients. Substantial underutilization of certain classes of cardioprotective medications is apparent, and systematic educational efforts in this direction may well prove worthwhile to impact outcomes.

Aged↗

PubMed2005

Chiral polyamines from reduction of polypeptides: asymmetric pyridoxamine-mediated transaminations.

BH3.THF can reduce polypeptides to polyamines with retention of chirality. The resulting polyamines are intriguing general platforms for asymmetric catalysis, given the diverse structures available and their relative ease of synthesis. We have constructed a number of chiral pyridoxamine catalysts based on reduced peptides. These compounds transaminate alpha-ketoacids with moderate to good enantioselectivity, while their peptidyl counterparts show almost no chiral induction.

Boranes↗

PubMed2005

Highly enantioselective phenylacetylene addition to aromatic ketones catalyzed by cinchona alkaloid-aluminum complexes.

The catalytic asymmetric addition of phenylacetylene to aromatic ketones is reported. The catalyst, generated from commercially available Cinchona alkaloids and industrially available triethylaluminum, gives the expected tertiary alcohols with good enantiomeric excess (70-89%) and yields (60-83%). No previous case has been reported successfully using triethylaluminum as a Lewis acid in the asymmetric alkynylation of carbonylic derivatives, and thus we provide a new method to obtain optically active tertiary propargyl alcohols.

Acetylene↗

PubMed2005

Cationic liposome-mediated bcl-xl gene transfection into human keratocytes.

The efficiency and safe range of Lipofectamine2000 (LF2000)/bcl-xl applied in human keratocytes, the optimal ratio of LF2000/bcl-xl and the bcl-xl gene expression in human keratocytes were investiaged. By using trypan-blue staining, the effects of LF2000 and bcl-xl on the survival rate of the cultured human keratocytes were measured respectively. By using semi-quantitative RT-PCR, the efficiency and the expression of LF2000-mediated bcl-xl transfection into keratocytes were examined. The results showed that the survival rate of human keratocytes had no signficant change in the presence of LF2000 (20 microg/ml) or bcl-xl (10 microg/ml) for 24 h. LF2000 could effectively mediate the transfection of exogenous gene bcl-xl into human keratocytes. The best transfection efficiency could be obtained when the ratio of bcl-xl/LF2000 was 1:8. One day after transfection, the positive cells for bcl-xl could be detectable, and the positive rate reached the peak-on the posttransfection day 3 (48.3%), then gradually decreased. Fifteen days after transfection, there were few positive cells. It was suggested that LF2000 could effectively transfer the exogenous gene bcl-xl into human keratocytes without obvious toxicity during a concentration range. LF2000/bcl-xl may be likely to play an important role in gene therapy of human keratocytes.

Cations↗

PubMed2005

Expression of exogenous or endogenous green fluorescent protein in adipose tissue-derived stromal cells during chondrogenic differentiation.

Pluripotent stem cells within the adipose stromal compartment, termed adipose-derived stromal cells (ASCs), have the potential to differentiate into a variety of cell lineages both in vitro and in vivo. Imaging with expression of exogenous or endogenous green fluorescent protein (GFP) reporters facilitates the detailed research on ASCs' physiological behavior during differentiation in vivo. This study was aimed to confirm whether ASCs expressing GFP still could be induced to chondrogenesis, and to compare the expression of exogenous or endogenous GFP in ASCs during chondrogenic differentiation. ASCs were harvested from inguinal fat pads of normal nude mice or GFP transgenic mice. Monolayer cultures of ASCs from normal mice were passaged three times and then infected with replication-incompetent adenoviral vectors carrying GFP genes. Allowed to recover for 5 days, Ad/GFP infected ASCs were transferred to chondrogenic medium as well as the ASCs from transgenic mice cultured in vitro over the same passages. The level of GFP in transgenic ASCs maintained stable till 3 months after chondrogenic induction. Whereas, high level of GFP expression in Ad/GFP infected ASCs could last for only 8 weeks and then declined stepwise. Important cartilaginous molecules such as SOX9, collagen type I, collagen type II, aggrecan, collagen type X were assessed using immunocytochemistry, RT-PCR, and Western Blot. The results indicated that no matter the GFP was exogenous or endogenous, it did not influence the chondrogenic potential of ASCs in comparison with the normal controls. Moreover, chondrogenic lineages from ASCs also underwent phenotypic modulation called dedifferentiation as a result of long-term culture in monolayers similar to normal chondrocytes.

Adipose Tissue↗

PubMed2005

The role of Akt on arsenic trioxide suppression of 3T3-L1 preadipocyte differentiation.

The present study investigates the molecular details of how arsenic trioxide inhibits preadipocyte differentiation and examines the role of Akt/PKB in regulation of differentiation and apoptosis. Continual exposure of arsenic trioxide, at the clinic achievable dosage that does not induce apoptosis, suppressed 3T3-L1 cell differentiation into fat cells by inhibiting the expression of PPARgamma and C/EBPalpha and disrupting the interaction between PPARgamma and RXRalpha, which determines the programming of the adipogenic genes. Interestingly, if we treated the cells for 12 or 24 h and then withdrew arsenic trioxide, the cells were able to differentiate to the comparable levels of untreated cells as assayed by the activity of GAPDH, the biochemical marker of preadipocyte differentiation. Long term treatment blocked the differentiation and the activity of GAPDH could not recover to the comparable levels of untreated cells. Continual exposure of arsenic trioxide caused accumulation in G2/M phase and the accumulation of p21. We found that arsenic trioxide induced the expression and the phosphorylation of Akt/PKB and it inhibited the interaction between Akt/PKB and PPARgamma . Akt/PKB inhibitor appears to block the arsenic trioxide suppression of differentiation. Our results suggested that Akt/PKB may play a role in suppression of apoptosis and negatively regulate preadipocyte differentiation.

3T3-L1 Cells↗

PubMed2005

Quality of life in chronic kidney disease (CKD): a cross-sectional analysis in the Renal Research Institute-CKD study.

BACKGROUND: Health-related quality of life (QOL) is an important measure of how disease affects patients' lives. Dialysis patients have decreased QOL relative to healthy controls. Little is known about QOL in patients with chronic kidney disease (CKD) before renal replacement therapy. METHODS: The Medical Outcomes Study Short Form-36 (SF-36), a standard QOL instrument, was used to evaluate 634 patients (mean glomerular filtration rate [GFR], 23.6 +/- 9.6 mL/min/1.73 m2 [0.39 +/- 0.16 mL/s/1.73 m2]) enrolled in a 4-center, prospective, observational study of CKD. SF-36 scores in these patients were compared with those in a prevalent cohort of hemodialysis (HD) patients and healthy controls (both from historical data). QOL data also were analyzed for correlations with GFR and albumin and hemoglobin levels in multivariable analyses. RESULTS: Patients with CKD had higher SF-36 scores than a large cohort of HD patients (P < 0.0001 for 8 scales and 2 summary scales), but lower scores than those reported for the US adult population (P < 0.0001 for 7 of 8 scales and 1 of 2 summary scales). Patients with CKD stage 4 had lower QOL scores than patients with CKD stage 5, although differences were not significant. Hemoglobin level was associated positively with higher mental and physical QOL scores (P < 0.05) in all individual and component scales except Pain. CONCLUSION: SF-36 scores were higher in this CKD cohort compared with HD patients, but lower than in healthy controls. GFR was not significantly associated with QOL. Hemoglobin level predicted both physical and mental domains of the SF-36. Longitudinal studies are needed to define at-risk periods for decreases in QOL during progression of CKD.

Black or African American↗

PubMed2005

Differential activation profiles of multiple transcription factors during dendritic cell maturation.

Immature dendritic cells (DC) at the environmental interfaces, such as the skin, constantly survey the tissue for the emergence of microbial products and pro-inflammatory mediators. Upon recognition of such "danger" signals, they undergo dynamic reprogramming of gene expression and functions, the process known as DC maturation, which plays critical roles in both innate and adaptive immune responses. Although DC have been shown to discriminate different maturation stimuli by expressing stimulus-specific signature genes and unique phenotypic and functional properties, underlying mechanisms for this extraordinary plasticity remain relatively unclear. We hypothesized that DC might activate unique sets of transcription factors (TF) upon sensing different stimuli. To test this hypothesis, we transduced a mouse epidermal-derived DC line XS106 to express the luciferase reporter gene under the control of each of 15 different cis-enhancer elements. The resulting DC panels were then exposed to 14 different microbial, endogenous, environmental, and pharmacological agents that produced unique maturational changes. This approach allowed systematic determination of TF activation profiles in DC. Our results revealed striking diversity, with different classes of stimuli triggering preferential activation of distinct sets of TF. We propose that differential TF usage represents a previously unrecognized mechanism regulating the direction of DC maturation.

Animals↗